Can Interferon Therapy Change the Natural Course of Hepatitis Delta Infection?: a Clinical and Pathological Study

Abstract

Chronic delta hepatitis (CDH) has a worse outcome than other types of viral hepatitis. High-dose, long-term alpha interferon (IFN-α) is the approved treatment and may ameliorate the course of infection. We evaluated long-term histological outcomes of CDH patients treated with IFN-α. Patients with histologically proved noncirrhotic CDH who were treated with high-dose IFN-α for at least 1 year were classified as cirrhotic or noncirrhotic at the end of treatment. Noncirrhotic patients also had posttreatment liver biopsies. Patients were designated histologically responsive or nonresponsive on the basis of fibrosis status. Histological, virological, and biochemical courses were analyzed. Forty-eight patients were treated with IFN-α (conventional and/or pegylated) for a median of 24 months with a posttreatment follow-up of 5 years. During the follow-up, cirrhosis developed in 24 patients, 5 of whom were decompensated. There was no difference between pre- and posttreatment fibrosis scores for 24 noncirrhotic patients at the end of follow-up. Among patients, 13% (n = 6) had decreased, 21% (n = 10) had steady, and 16% (n = 8) had increased fibrosis scores. Persistent viral response (PVR) was achieved in 16 patients (33%). Twenty percent of the entire group was histologically responsive (decreasing or steady fibrosis scores with improved necroinflammatory scores), while nearly 80% had histological progression/cirrhosis. PVR was significantly associated with histological response. The long-term natural course of patients who were treated with high dose IFN-α for at least 1 year was evaluated clinically and histologically. Despite the association of PVR with histological response, IFN-α treatment did not change the natural course of CDH; clinical and histological progression continued in two-thirds of the cases despite treatment.

Keywords: cirrhosis; hepatitis delta; histology; interferon alpha; natural course.

FIG 1

Follow-up diagram for the study group. Half of the patients were cirrhotic after the median 21-month treatment period. Six patients had decreased, 10 patients had stable, and 8 patients had increased fibrosis scores in the posttreatment noncirrhotic patient group. Overall, 38 of 48 patients were histologically nonresponsive despite treatment.

FIG 2

Comparison of mean pre- and posttreatment fibrosis scores (FS) of patients grouped according to posttreatment fibrosis status.

FIG 3

Persistent virological response (PVR) rates among patients with different histological outcomes. PVR rate was 70% for histological responders and 23% for histological nonresponders (P = 0.005). Seventeen percent of cirrhotic patients also had PVR.